Drugs, xenobiotics and endogenous products of biosynthetic and catabolic pathways are metabolized by processes that regulate their action and toxicity. The formation of glucuronides catalyzed by UDP-glucuronyltransferase activities in hepatic endoplasmic reticulum is a major means of biotransformation and is important for the termination of action of morphine and certain hormones such as estrogens. Previous studies from this laboratory showed that separate enzymes for metabolism through glucuronidation exist and the current studies that are proposed are designed to extend these observations. Morphine and estrone UDP-glucuronyltransferase activities will be isolated and their substrate specificities will be studied. Inhibitors will be evalutated toward both enzymes as will properties of the basic nature of these proteins (kinetic properties, molecular size, phospholipid assoication). Information derived from in vitro studies will be applied to an understanding of the metabolism of these agents in vivo. Developmental aspects of the enzymes will be approached once basic information is gathered. Other enzymes of this class such as that involved in p-nitrophenol glucuronidation will be studied in conjunction with morphine and estrone transferases as a guide to enzyme separation and for possible future understanding with respect to multiplicity of transferases as a guide to enzyme separation and for possible future understanding with respect to multiplicity of transferases and for explanation of possible role in the toxicology of these types of substances. Through this work it is hoped that a clear understanding of the regulation of the pharmacology and toxicology of drugs and xenobiotics is appreciated and that pathophysiologic states where inordinate concentrations of certain endogenous metabolites occur may be alleviated.